Safety and efficacy of the cyclooxygenase-2 inhibitors parecoxib and valdecoxib after noncardiac surgery.

Background: Valdecoxib and its intravenous prodrug parecoxib are reported to increase thromboembolic risk after coronary artery bypass grafting. The authors conducted a randomized trial to examine their safety and analgesic efficacy in patients recovering from major noncardiac surgical procedures.

Methods: The trial was randomized and double-blind, with 10 days of treatment and 30 days of follow-up. Patients (n = 1,062) received either parenteral parecoxib for 3 days and oral valdecoxib for the rest of the treatment period or placebo medications throughout. The frequency of predefined adjudicated postrandomization adverse events, including cardiovascular thromboembolism, renal dysfunction, gastroduodenal ulceration, and wound-healing complications, was assessed in each group. Secondary efficacy endpoints included patients' pain ratings, opioid analgesic consumption (recorded as morphine equivalents), and reports of opioid-related adverse effects.

Results: Predefined adjudicated adverse events had similar frequencies among patients who received parecoxib and valdecoxib (2.7%) and placebo patients (3.2%) (P = 0.58), including cardiovascular thromboembolic events (1.0% in each group; P = 1.0). Placebo patients consumed more morphine equivalents (66.2 +/- 92.4 mg) than did patients receiving parecoxib and valdecoxib (43.2 +/- 65.7 mg) (P < 0.001). Placebo patients had higher mean pain ratings on each of study days 2-10 (P < 0.01) and reported more opioid-related symptom distress on days 2-6 (P < 0.01).

Conclusions: Parecoxib and valdecoxib are useful adjuncts to opioids for the treatment of postoperative pain in noncardiac surgical patients. Further study will be required to determine the safety profile of parecoxib and valdecoxib administered to patients with known atherosclerotic disease after noncardiac surgery.